Hydrochloric Acid → 1-benzyl-N-[(2-nitrophenyl)methyl]piperidin-4-amine

HRID 239108Notes

Reaction equation

HRID 239108 reaction equation
[N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=O)([O-:3])=[O:2].[NH2:12][CH:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:15][CH2:14]1.[BH4-].[Na+].Cl.[OH-].[Na+]>CO.O>[CH2:19]([N:16]1[CH2:17][CH2:18][CH:13]([NH:12][CH2:6][C:5]2[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=2[N+:1]([O-:3])=[O:2])[CH2:14][CH2:15]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 111012-NitrobenzaldehydeHCID 14798Sodium HydroxideHCID 4158521-Benzyl-4-piperidylamineHCID 4311764Sodium borohydride

Product 1

HCID 48487621-benzyl-N-[(2-nitrophenyl)methyl]piperidin-4-amineYield 99.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

5955 g 2-nitrobenzaldehyde was suspended in 10 L methanol under nitrogen atmosphere and 7500 g 4-amino-1-benzyl-piperadine in 5 L methanol was added over 30 min. The reaction was stirred 1 h at RT. The reaction mixture was cooled to 0° C. and a cold solution of 1044 g sodium borohydride in 6425 mL water was added at a rate to keep the temperature below 10° C. After 1 h stirring at 0° C. and 1 h at RT the reaction was cooled again to 0° C. and aqueous 4 mol/L hydrochlorid acid was added. Then the reaction mixture was stirred at RT for 30 min and cooled again to 0-10° C. Aqueous 5 mol/L sodium hydroxide solution was added until pH=14 and the reaction was extracted with tert-butyl methylether. The organic layer was washed with water and saturated sodium chloride solution and the solvent was evaporated. The residue was dissolved in toluol, filtered and concentrated again to yield 12.8 kg of the desired product.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. customthe temperature below 10° C
  3. stirringAfter 1 h stirring at 0° C. and 1 h at RT the reaction
  4. temperaturewas cooled again to 0° C.
  5. stirringThen the reaction mixture was stirred at RT for 30 min
  6. temperaturecooled again to 0-10° C
  7. extractionthe reaction was extracted with tert-butyl methylether
  8. washThe organic layer was washed with water and saturated sodium chloride solution
  9. customthe solvent was evaporated
  10. dissolutionThe residue was dissolved in toluol
  11. filtrationfiltered
  12. concentrationconcentrated again

Sources & evidence

ORD record
ord-e09f06aff0cc4ca0aef95b2fcd84aae2
Source dataset
uspto-grants-2014_02
Patent number
US08642774B2

Reaction notes

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